6hg9

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<StructureSection load='6hg9' size='340' side='right'caption='[[6hg9]], [[Resolution|resolution]] 3.62&Aring;' scene=''>
<StructureSection load='6hg9' size='340' side='right'caption='[[6hg9]], [[Resolution|resolution]] 3.62&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6hg9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HG9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HG9 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6hg9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HG9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HG9 FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6hg4|6hg4]]</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.62&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6hg9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hg9 OCA], [http://pdbe.org/6hg9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hg9 RCSB], [http://www.ebi.ac.uk/pdbsum/6hg9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hg9 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6hg9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hg9 OCA], [https://pdbe.org/6hg9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hg9 RCSB], [https://www.ebi.ac.uk/pdbsum/6hg9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hg9 ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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<div style="background-color:#fffaf0;">
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[[http://www.uniprot.org/uniprot/IL17F_HUMAN IL17F_HUMAN]] Defects in IL17F are the cause of familial candidiasis type 6 (CANDF6) [MIM:[http://omim.org/entry/613956 613956]]. CANDF6 is a rare disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.<ref>PMID:21350122</ref> [[http://www.uniprot.org/uniprot/I17RC_HUMAN I17RC_HUMAN]] Chronic mucocutaneous candidiasis. The disease is caused by mutations affecting the gene represented in this entry.
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== Publication Abstract from PubMed ==
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== Function ==
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Interleukin-17A (IL-17A), IL-17F, and IL-17A/F heterodimers are key cytokines of the innate and adaptive immune response. Dysregulation of the IL-17 pathway contributes to immune pathology, and it is therefore important to elucidate the molecular mechanisms that govern IL-17 recognition and signaling. The receptor IL-17RC is thought to act in concert with IL-17RA to transduce IL-17A-, IL-17F-, and IL-17A/F-mediated signals. We report the crystal structure of the extracellular domain of human IL-17RC in complex with IL-17F. In contrast to the expected model, we found that IL-17RC formed a symmetrical 2:1 complex with IL-17F, thus competing with IL-17RA for cytokine binding. Using biophysical techniques, we showed that IL-17A and IL-17A/F also form 2:1 complexes with IL-17RC, suggesting the possibility of IL-17RA-independent IL-17 signaling pathways. The crystal structure of the IL-17RC:IL-17F complex provides a structural basis for IL-17F signaling through IL-17RC, with potential therapeutic applications for respiratory allergy and inflammatory bowel diseases.
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[[http://www.uniprot.org/uniprot/IL17F_HUMAN IL17F_HUMAN]] Stimulates the production of other cytokines such as IL-6, IL-8 and granulocyte colony-stimulating factor, and can regulate cartilage matrix turnover. Stimulates PBMC and T-cell proliferation. Inhibits angiogenesis. [[http://www.uniprot.org/uniprot/I17RC_HUMAN I17RC_HUMAN]] Receptor for IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RA (PubMed:16785495). Receptor for the heterodimer formed by IL17A and IL17B as part of a heterodimeric complex with IL17RA (PubMed:18684971). Has also been shown to be the cognate receptor for IL17F and to bind IL17A with high affinity without the need for IL17RA (PubMed:17911633). Activation of IL17RC leads to induction of expression of inflammatory chemokines and cytokines such as CXCL1 (PubMed:16785495).<ref>PMID:16785495</ref> <ref>PMID:17911633</ref> <ref>PMID:18684971</ref> Receptor for both IL17A and IL17F.<ref>PMID:16785495</ref> Does not bind IL17A or IL17F.<ref>PMID:16785495</ref> Does not bind IL17A or IL17F.<ref>PMID:16785495</ref> Receptor for both IL17A and IL17F.<ref>PMID:16785495</ref>
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Structural Analysis Reveals that the Cytokine IL-17F Forms a Homodimeric Complex with Receptor IL-17RC to Drive IL-17RA-Independent Signaling.,Goepfert A, Lehmann S, Blank J, Kolbinger F, Rondeau JM Immunity. 2020 Mar 17;52(3):499-512.e5. doi: 10.1016/j.immuni.2020.02.004. PMID:32187518<ref>PMID:32187518</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6hg9" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Interleukin 3D structures|Interleukin 3D structures]]
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*[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Goepfert, A]]
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[[Category: Goepfert A]]
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[[Category: Rondeau, J M]]
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[[Category: Rondeau JM]]
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[[Category: Cystine-knot]]
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[[Category: Fniii domain]]
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[[Category: Immune system]]
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[[Category: Receptor-cytokine complex]]
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Current revision

Crystal Structure of the human IL-17RC ECD in complex with human IL-17F, Crystal form II

PDB ID 6hg9

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